CDR-GRAFTED ANTIBODY FOR RADIOIMMUNOTHERAPY OF LYMPHOMA

用于淋巴瘤放射免疫治疗的 CDR 移植抗体

• 批准号: 2517616
• 负责人: GARY Leonard GRIFFITHS
• 金额: $ 39.67万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-10 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517616
• 关键词: antitumor antibody; athymic mouse; clinical research; clinical trials; high performance liquid chromatography; human subject; human therapy evaluation; indium; iodine; method development; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy; nonHodgkin's lymphoma; nonhuman therapy evaluation; pharmacokinetics; radionuclides; yttrium

The aim of this work is to produce a clinically useful, commercially viable, new therapy agent against Non-Hodgkin's Lymphoma. Radioimmunotherapy has shown clinical efficacy against B-cell lymphoma in the last few years, and shows promise of becoming a completely new treatment modality for this disease. We will produce a Y-90 radiolabeled, humanized, anti-CD22 antibody, Y-90-hLL2, which can be practically manufactured, kit-formulated, radiolabeled and used. The product will take advantage of the internalizing properties of the hLL2 mab, bear a residualizing radiolabel, be designed with minimum potential for patient immune response, and ultimately, could be useful on an out-patient basis. Phase II work will determine the best option for the Y-90-hLL2 product from the several putative agents, by studying the properties of each with respect every aspect of the subject, including: Preparative ease, kit stability, radiolabeling efficiency, post-labeling product stability including radiolysis concerns, potential for immunogenicity, cellular binding/retention properties, animal pharmacokinetics, and clinical-use viability. From this, the chosen agent will be taken to a clinical phase I study to establish human targeting, dosimetry, the maximum tolerated dose of the agent, and preliminary efficacy. POTENTIAL COMMERCIAL APPLICATION: There are not good treatment options for patients with relapsed B-cell lymphoma, and patients are often stricken in their middle years, making societal costs heavy. This disease, of steadily increasing incidence, is responsive to radiation, including antibody-targeted radiation. If our advanced antibody-targeted yttrium-90 agent can be shown to have efficacy in this work against some of the sickest of patients, our agent could eventually find widespread application as a new, complementary modality. Then, use at an earlier, more responsive, disease stage may be feasible.

这项工作的目的是生产临床上有用的，商业上 对非霍奇金淋巴瘤的可行，新的治疗剂。 放射免疫疗法已显示针对B细胞淋巴瘤的临床功效 最近几年，并表现出成为全新的希望 该疾病的治疗方式。我们将产生Y-90放射性标记， 人性化的，抗CD22抗体，Y-90-HLL2，实际上可以是 制造，套件形成，放射标记和使用。产品将采用 HLL2 mAb的内部化特性的优势，带有A 降级放射性标记，设计为患者的潜力最小 免疫反应，最终可能会在门诊中有用。 第二阶段的工作将确定Y-90-HLL2产品的最佳选择 从几种推定的代理中，通过研究每个代理的特性 尊重主题的各个方面，包括：准备易于，套件 稳定性，放射标记效率，标签后产品稳定性 包括辐射溶解问题，免疫原性的潜力，细胞 结合/保留特性，动物药代动力学和临床使用 生存能力。由此，所选的代理将被带到临床I期 研究建立人类靶向剂量法，最大耐受剂量的研究 代理和初步功效。 潜在的商业应用：没有好的治疗选择 对于复发性B细胞淋巴瘤的患者，患者通常是 在中期，社会成本很高。这种疾病， 发病率不断增加，对辐射有反应，包括 抗体靶向辐射。如果我们的先进抗体靶向YTTrium-90 可以证明代理在这项工作中具有功效 最病的患者，我们的经纪人最终可能会发现广泛 应用是一种新的互补方式。然后，在早期使用 更敏感的疾病阶段可能是可行的。